Kulkarni P S, Hamid H, Barati M, Butulija D
Department of Ophthalmology and Visual Sciences, School of Medicine, University of Louisville, Kentucky 40202, USA.
Invest Ophthalmol Vis Sci. 1999 Mar;40(3):721-8.
To unmask the vasoconstricting effect of angiotensin II (Ang II) on retinal smooth muscle by studying its interaction with endothelium-derived paracrine substances. This study focused specifically on determining the changes in vascular diameter and the release of endothelial-derived vasodilators, nitric oxide (NO) and prostaglandin (PG) I2, from isolated retinal microvessels.
Bovine retinal central artery and vein were cannulated, and arterioles and venules were perfused with oxygenated/heparinized physiological salt solution at 37 degrees C. This ex vivo perfused retinal microcirculation model was used to observe the contractile effects of Ang II on arterioles and venules of different diameters. The NO and PGI2 synthase inhibitors, 1-NOARG and flurbiprofen, respectively, were used to unmask Ang II vasoconstriction; the changes in vascular diameters were then measured. Enzyme immunoassays were used to measure the release of cGMP (an index of NO release) and 6-keto-PG-F1alpha (a stable metabolite of PGI2) from isolated bovine retinal vessels.
Topically applied Ang II (10(-10) M to 10(-4) M) caused significant (P < 0.05) arteriolar and venular constrictions in a dose-dependent manner, with the smallest retinal arterioles (7+/-0.2 microm luminal diameter) and venules (12+/-2 microm luminal diameter) significantly more sensitive than larger vessels. After the inhibition of endogenous NO and PGI2 synthesis by 1-NOARG and flurbiprofen, respectively, the vasoconstriction effects of Ang II became more pronounced. Again, the smallest vessels tested were significantly more sensitive, and synthesis of endothelial-derived relaxing factor (EDRF), therefore, may be most important in these vessels. Vasoactive doses of Ang II (10(-10) M to 10(-4) M) caused a dose-dependent increase in the release of NO and PGI2 from isolated bovine retinal vessels, indicating that the increase in EDRF may nullify direct Ang II-induced vasoconstriction. Interestingly, intraluminal administration of Ang II caused only vasodilation.
This study demonstrates that the retinal vascular endothelium acts as a buffer against the vasoconstricting agent Ang II via release of vasodilators NO and PGI2, and the vasoconstriction effects due to Ang II are most prominent in the smallest diameter vessels.
通过研究血管紧张素II（Ang II）与内皮源性旁分泌物质的相互作用，揭示其对视网膜平滑肌的血管收缩作用。本研究特别关注确定血管直径的变化以及从分离的视网膜微血管中释放内皮源性血管舒张剂一氧化氮（NO）和前列腺素（PG）I2的情况。
将牛视网膜中央动脉和静脉插管，在37℃下用含氧/肝素化的生理盐溶液灌注小动脉和小静脉。使用这种离体灌注视网膜微循环模型观察Ang II对不同直径小动脉和小静脉的收缩作用。分别使用NO和PGI2合酶抑制剂1-NOARG和氟比洛芬来揭示Ang II的血管收缩作用；然后测量血管直径的变化。使用酶免疫测定法测量从分离的牛视网膜血管中释放的cGMP（NO释放的指标）和6-酮-PG-F1α（PGI2的稳定代谢产物）。
局部应用Ang II（10^(-10) M至10^(-4) M）以剂量依赖性方式引起显著（P < 0.05）的小动脉和小静脉收缩，最小的视网膜小动脉（管腔直径7±0.2微米）和小静脉（管腔直径12±2微米）比较大的血管明显更敏感。分别用1-NOARG和氟比洛芬抑制内源性NO和PGI2合成后，Ang II的血管收缩作用变得更加明显。同样，所测试的最小血管明显更敏感，因此内皮源性舒张因子（EDRF）的合成在这些血管中可能最为重要。血管活性剂量的Ang II（10^(-10) M至10^(-4) M）导致从分离的牛视网膜血管中释放的NO和PGI2呈剂量依赖性增加，表明EDRF的增加可能抵消直接由Ang II诱导的血管收缩。有趣的是，管腔内给予Ang II仅引起血管舒张。
本研究表明，视网膜血管内皮通过释放血管舒张剂NO和PGI2作为对抗血管收缩剂Ang II的缓冲，并且Ang II引起的血管收缩作用在最小直径的血管中最为突出。
